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Alzheimer's Disease Health Center

Lithium May Be Alzheimer's Treatment

Bipolar Drug Keeps Mouse Brains Free of Damaging Plaque
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May 21, 2003 -- A drug used for 50 years to fight bipolar disorder might become the newest Alzheimer's treatment.

New studies show that lithium -- at doses similar to those used to treat bipolar disorder -- prevents Alzheimer's disease in mice. A report on the experiments, conducted at the University of Pennsylvania lab of Peter Klein, MD, PhD, appears in the May 22 issue of the journal Nature.

People with Alzheimer's disease get a buildup of plaque outside nerve cells in the brain. They also get a buildup of fiber-like "tangles" inside brain cells. Lithium blocks an enzyme -- GSK-3 -- crucial to the development of both the plaque and the tangles.

"A therapeutic dose of lithium markedly reduces" brain levels of plaque, Klein and colleagues report. Painkillers in the aspirin family -- known as NSAIDs -- fight plaque in a different way. "Combination therapy with lithium and NSAIDs could have an enhanced effect in reducing [plaque]," the researchers suggest.

The idea is still very much experimental. In a commentary accompanying the Klein team's report, two Alzheimer's experts warn that blocking the GSK-3 enzyme could have unwanted side effects. One of these might be intestinal cancer, warn Bart De Strooper, MD, PhD, of Catholic University in Leuven, Belgium, and James Woodgett, PhD, of the University of Toronto in Ontario, Canada. However, no link has been found between intestinal cancer and lithium, which has been used for many years to treat bipolar disorder.

Younger patients who take lithium usually get over its side effects. But these side effects are worse in elderly patients. And lithium can be a dangerous drug. Just a little bit too much can damage the kidneys. For these reasons, the Klein team, De Strooper, and Woodgett suggest that it would be a good idea to develop safer GSK-3 inhibitors.

"GSK-3 inhibitors could be an attractive addition to the list of candidate drugs for preventing [Alzheimer's] plaques -- with the potential benefit of inhibiting the formation of tangles, too," De Strooper and Woodgett write.

SOURCE: Nature, May 22, 2003.

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